Point-of-care nano zinc oxide carbon paste sensor for non-invasive determination of clozapine in saliva samples

Clozapine (CLZ); an atypical antipsychotic drug, is well known to have a significant role in managing schizophrenic patients with substance use disorder (SUD). Unfortunately, many patients are deprived of CLZ benefits due to its limited prescription. This is based upon concerns regarding the critical side effects of CLZ in case of overdosing especially, with the lack of accessible therapeutic drug monitoring (TDM) tools. In this contribution, a simple, accurate and sensitive electrochemical method is proposed for CLZ assay in human saliva. Unlike previously reported methods for TDM of CLZ that depends on invasive matrices as plasma and urine, this method employs electrochemical approaches in exploring human saliva as a patient-friendly alternative for assessing CLZ. The proposed method employs differential pulse voltammetry (DPV) with a sensitive and selective Ag-doped ZnO nanoparticles based carbon paste electrode (CPE). The adopted electrochemical sensor has not been previously reported for CLZ determination, despite it offers enhanced sensitivity together with simple synthesis. The synthesized nanoparticles were characterized through Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The developed sensor was optimized and validated as per FDA guidelines of bioanalytical methods. The linear range in saliva was 0.31-3.67 µmol/L and the lower limit of quantitation (LLOQ) was 0.31 µmol/L. The high reliability and applicability of the suggested method has strong potential to be integrated in a point-of-care testing (POCT) device to introduce more accessible TDM that enables smooth TDM of CLZ. Therefore, it opens pathways for broader and safe use of CLZ.